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Distinct spatial expression patterns of AP-2alpha and AP-2gamma in non-neoplastic human breast and breast cancer.

Although transcription factors AP-2alpha and AP-2gamma have been implicated in the control of estrogen receptor (ER) and ErbB-2, their impact for breast cancer is still controversial. To better understand the role of AP-2 proteins in mammary neoplasia, the analysis of their spatial expression pattern in normal breast and breast cancer is required. A total of 51 specimens of female breast cancer patients and a tissue microarray containing 93 additional female breast cancer cases were immunohistochemically stained for AP-2alpha, AP-2gamma, ER and ErbB-2. In 70 cases of the tissue microarray, survival data comprising a period of up to 30 years were present. In non-neoplastic breast tissue, AP-2alpha was expressed in the inner glandular cell layer while AP-2gamma was expressed in the outer myoepithelial cell layer. Ductal carcinoma in situ revealed strongly AP-2alpha-positive tumor cells surrounded by a layer of AP-2gamma-positive myoepithelial cells. In invasive carcinoma, expression of AP-2alpha and AP-2gamma was variable. High expression of ER and AP-2alpha showed better survival rates than low expression of these markers. AP-2gamma expression had no effect on survival. These results for the first time reveal a distinct spatial expression pattern of AP-2alpha and AP-2gamma in normal breast and in ductal carcinoma in situ with specific AP-2gamma expression in myoepithelium. High ER and AP-2alpha expression in invasive breast cancer showed favorable survival rates. Therefore, AP-2alpha expression seems to be associated with better prognosis of breast cancer. AP-2gamma expression has no influence on survival reflecting that myoepithelial cells are not involved in the neoplastic process.

Actins↗

Distortion of spatial selectivity by pattern onset stimulation.

Spatial selectivity of pattern evoked potentials has been thought to provide evidence of lateral inhibition. However, spatial tuning functions may be distorted by pattern onset stimulation that is applied repeatedly to the same area of retina so an after-image is formed. This only applies at low spatial frequencies because of the randomizing effects of eye movements. Low-frequency attenuation may therefore be exaggerated. Pattern reversal stimulation has the opposite effect and this is reflected in the literature by fewer reports of bandpass functions. A new method has therefore been devised to provide the true spatial response function. The spatial phase is reversed after every two consecutive presentations. By combining this paradigm with a correction for the optical transfer function of the eye, the true neural response function is obtained. Ten subjects participated in this study to evaluate the distortion of spatial selectivity in the pattern electroretinogram. The new stimulus paradigm reduced the low spatial frequency attenuation to a barely significant level giving an almost flat amplitude response for the + ve and - ve transients of the pattern electroretinogram for check sizes from 222' to 7' angular subtense. However, correction for optical degradation produces bandpass curves, which closely correspond to those predicted from recent data on receptive fields of primate retinal ganglion cells.

Adult↗

A behavioral assessment of hippocampal function based on a subregional analysis.

The purpose of this review is to determine whether specific subregions (dentate gyrus [DG], CA3, and CA1) of the hippocampus provide unique contributions to specific processes associated with intrinsic information processing exemplified by novelty detection, encoding, pattern separation, pattern association, pattern completion, retrieval, short-term memory and intermediate-term memory. Based on anatomical neural network organization, electrophysiology of cellular activity, lesions, early gene activation, and computational modeling, it can be shown that there exists extensive cooperation among the three subregions of the hippocampus, but there also exists reliable specificity of function for each of the subregions of the hippocampus. The primary process supported by the DG subregion of the hippocampus can be characterized by orthogonalization of sensory inputs to create a metric spatial representation. Furthermore the DG participates in conjunction with CA3 in supporting spatial pattern separation. The CA3 subregion of the hippocampus supports processes associated with spatial pattern association, spatial pattern completion, novelty detection, and short-term memory. The CA1 subregion of the hippocampus supports processes associated with temporal pattern association, temporal pattern completion, and intermediate-term memory. Furthermore, the CA3 in conjunction with CA1 supports temporal pattern separation. All the above-mentioned processes are assumed to reflect intrinsic processing of information within the hippocampus. The diversity of functions associated with the different subregions of the hippocampus suggests that one should not treat the hippocampus as a single entity, but rather that one should concentrate on elucidating further the functions of both dorsal and ventral subregions of the hippocampus and pathways that directly connect each of the subregions as well as their connections with the entorhinal cortex.

Animals↗

Backward masking of lateralized faces by noise, pattern, and spatial frequency.

Experiments 1 and 2 measured the critical interstimulus interval at which a face presented to the right or left visual field escaped a trailing noise, pattern, or spatial-frequency mask. The function relating target duration to critical ISI was multiplicative in the noise and spatial-frequency condition, but additive at longer durations in the pattern mask condition. An advantage of about 8 msec for the left visual field and 2 msec for the right field was found in the pattern and spatial-frequency masking condition, respectively. No consistent visual field differences were found in the noise mask condition. Taken together, these results suggest that hemispheric difference in face recognition are either absent or inconsistent at early, peripheral, energy-sensitive stages of processing, but emerge strongly at higher order central stages. The results also suggest that the left and right hemispheres are not differentially sensitive to the output of high- and low-spatial-frequency channels, respectively. If it is assumed that the central face processor is functionally localized to the right hemisphere, one can infer from these results that interhemispheric transmission time is not greater than 8 msec, and the output of sensory analysis and/or relational features are transferred across the interhemispheric commissures.

Adolescent↗

On rugged shape of skin tumor (basal cell carcinoma).

Basal cell carcinoma (BCC) is the most common cancer of the skin that is made of transformed basal cells of the human epidermis, and spreads along the epidermis--dermis junction. It often forms tumor cell mass that protrudes towards the dermal connective tissue with many branches. Histopathological examination of the cancer demonstrates the cell mass of a rugged shape appearing as many regular spaced islands in a two-dimensional section. We study the process of cell proliferation and spatial pattern formation of the skin tumor by a pair of partial differential equations of tumor cells and nutrients. The assumptions are: (1) proliferation rate of tumor cells depends on the availability of nutrients, which simply diffuse out of capillaries through connective tissue; (2) nutrients are consumed by active tumor cells; (3) cell diffusion coefficient expressing tumor cell movements increase with the cell density and the nutrient availability. Starting from the initial condition with a single layer of tumor cells. the model develops a smooth colony if n'0 is large, but a characteristic rugged spatial pattern of tumor cell mass if n'0 is small, in which n'0 is nutrient concentration multiplied by square root of growth efficiency divided by diffusion coefficient of nutrients. The proportion of the area occupied by tumor cells increases with n'0. The coefficient of variation in the width of "islands" of tumor cell mass is rather small (0.2 reverse similar0.6), implying the regularity of the spatial pattern. We also analyses the photographs of a two-dimensional section of tumor cell mass and compare the spatial patterns generated by the model.

Aged↗

Temporal and spatial expression patterns of FoxN genes in Xenopus laevis embryos.

Using RT-PCR and in situ hybridisation, we have analysed the temporal and spatial expression patterns of Xenopus Fox genes of subclass N. By screening cDNA libraries and by RT-PCR using embryonic RNA and primers derived from EST analyses, we could isolate FoxN2, FoxN4, FoxN5 and different isoforms of FoxN3. FoxN2 and FoxN3 transcripts were found during all developmental stages including early cleavage and tailbud stages. FoxN5 transcripts were only present at early cleavage stages, while FoxN4 expression began after midblastula transition. Spatial expression of FoxN2 was first detected in the early eye field and later, in the branchial arches, the vagal ganglion and in the developing retina. FoxN3 transcripts were found within the animal cap. In post-gastrula embryos, neural crest cells and the early eye field showed strong expression of FoxN3. At late tadpole stages, the branchial arches were stained. FoxN4 was expressed in the early eye field and later in the developing retina cells, the nephrostomes of the pronephric kidney and in the midbrain. A ubiquitous expression of FoxN5 was found in early cleavage stage embryos.

Amino Acid Sequence↗

Frequency-specific interaural level difference tuning predicts spatial response patterns of space-specific neurons in the barn owl inferior colliculus.

Space-specific neurons in the barn owl's inferior colliculus have spatial receptive fields (RFs) because of sensitivity to interaural time difference and frequency-specific interaural level difference (ILD). These neurons are assumed to be tuned to the frequency-specific ILDs occurring at their spatial RFs, but attempts to assess this tuning with traditional narrowband stimuli have had limited success. Indeed, tuning assessed in this manner, when processed via a linear model of spectral integration, typically explains only approximately half the variance in spatial response patterns. Here we report our findings that frequency-specific ILD tuning of space-specific neurons, when assessed from responses to broadband stimuli, predicted nearly 75% of the variance in spatial responses, using a linear model of spectral integration (p < 0.0001; n = 97 neurons). Furthermore, when we tested neurons using only those frequencies we found to be spatially relevant, we saw that their responses were similar to those elicited by broadband stimuli. When we used frequencies not identified as spatially relevant, such similarity was lacking. Furthermore, spectral components that elicited high firing rates when presented as narrowband stimuli were found in several cases to be irrelevant for or detrimental to the definition of spatial RFs. Thus, neurons achieved sharp spatial tuning by selecting for ILDs of a subset of spectral components in noise, some of which were not identified using narrowband stimuli.

Acoustic Stimulation↗

Biomonitoring using the lichen Hypogymnia physodes and bark samples near Zlatna, Romania immediately following closure of a copper ore-processing plant.

Lichen transplants were established along a 40km transect centred on a large mine waste dump close to Zlatna town centre, two weeks after closure of a major industrial source, to compare spatial patterns of element concentrations in lichen and bark samples. After 3 months of exposure, spatial patterns of 4 element concentrations (Pb, Cu, Zn and Fe) in transplants confirmed deposition due to a point source 'Zlatna influence'. Cu and Pb reached concentrations 8 and 4 times, respectively, higher than samples transplanted in the 'background' site, and over 200 (Cu) and 2000 (Pb) times higher relative to 'background' bark. Ten out of 15 elements analysed reached highest concentrations in bark. Spatial patterns confirmed long-term pollution for 6 elements (Pb, S, Fe, Cu, Zn and Ba). The study provides a model baseline to monitor recovery following closure of major industrial sources and highlights the importance of considering biogeochemical processes when interpreting metal concentrations.

Betulaceae↗

Adaptive plasticity of the auditory space map in the optic tectum of adult and baby barn owls in response to external ear modification.

1. This study demonstrates the influence of experience on the establishment and maintenance of the auditory map of space in the optic tectum of the barn owl. Auditory experience was altered either by preventing the structures of the external ears (the facial ruff and preaural flaps) from appearing in baby barn owls (baby ruff-cut owls) or by removing these structures in adults (adult ruff-cut owls). These structures shape the binaural cues used for localizing sounds in both the horizontal and vertical dimensions. 2. The acoustic effects of removing the external ear structures were measured using probe tube microphones placed in the ear canals. In both baby and adult ruff-cut owls, the spatial pattern of binaural localization cues was dramatically different from normal: interaural level difference (ILD) changed with azimuth instead of with elevation, the rate of change of ILD across space was decreased relative to normal, and the rate of change of interaural time difference (ITD) across frontal space was increased relative to normal. 3. The neurophysiological representations of ITD and ILD in the optic tectum were measured before and > or = 3 mo after ruff removal in adults and beginning at 4.5 months of age in baby ruff-cut owls. Multiunit tuning to ITD and to ILD was measured using dichotic stimulation in ketamine-anesthetized owls. The tectal maps of ITD and ILD were reconstructed using visual receptive field location as a marker for recording site location in the optic tectum. 4. Adjustment of the tectal map of ITD to the altered spatial pattern of acoustic ITD was essentially complete in adults as well as in baby ruff-cut owls. This adjustment changed the magnification of ITD across the tectum, with resultant changes in ITD tuning at individual tectal sites of up to approximately 25 microseconds (approximately 5% of the physiological range) relative to normal values. 5. Adaptation of the tectal ILD map to the ruff-cut spatial pattern of acoustic ILD was substantial but clearly incomplete in both adult and baby ruff-cut owls. Although changes of up to approximately 15 dB (approximately 47% of the physiological range) relative to normal tuning were observed at certain tectal sites, the topography of the ILD map was always intermediate between normal and that predicted by the ruff-cut spatial pattern of acoustic ILD.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Role of chaotic dynamics in neural plasticity.

Mathematical models are essential for the study of complex neural systems at all levels of the hierarchy from macromolecules through neurons to brain systems. ANN are readily available, but most of them are inappropriate for modeling brain function in normal behavior, because they stem from studies of neural systems in anesthetized or paralyzed animals which are capable only of reflux output. That class of models lacks the goal-directed, self-organizing properties of neural systems in behaving animals. In contrast to the stability of ANN and their reliance on asymptotic convergence to steady states (point attractors) and periodic oscillations (limit cycle attractors), BNN are intrinsically unstable. They continuously generate 'spontaneous' aperiodic activity that manifests the operation of chaotic dynamics undergoing repeated state transitions. Observations on the activity patterns of sensory cortex reveal that the perceptual outputs of BNN are by construction of spatial patterns and dynamic trajectories and not by computation using symbolic representations. Chaotic dynamics plays essential roles both in the construction of perceptions and in the continuing update of cortical populations, which requires selective synaptic modification during associative learning and habituation. Simultaneous multichannel recording from the olfactory bulb and cortex has given the following experimental results. (1) The cortical activity that relates to the perception of a sensory stimulus is carried macroscopically by a smaller number of single neurons e.g. 'units', 'feature detectors'. (2) The macroscopic activity reflects the meaning and significance of the stimulus for the experimental subject and not the stimulus as it is known to the observer. (3) The activity carries the meaning in spatial patterns, not in time series (the difference between a phonograph or radio and movie or TV). (4) The spatial patterns of activity that accompany previously learned stimuli or responses are changed by the introduction of new stimuli and also by modifications in reinforcement contingencies. There is no invariance in the memory store within the populations. (5) The patterns of activity are created by dynamic neural interactions in sensory cortex, not by registration or filtering of stimuli. There is no evidence for storage, retrieval, cross-correlation or logical tree search. (6) The dynamics is chaotic, not merely noisy, so that each act of perception involves a new construction by the cortex not by mere information processing. From these findings we infer that chaotic dynamics plays a crucial role in the construction of the associational contexts comprising the memory systems of experimental subjects.

Animals↗

[Statistical models for spatial analysis in parasitology].

The simplest way to study the spatial pattern of a disease is the geographical representation of its cases (or some indicators of them) over a map. Maps based on raw data are generally "wrong" since they do not take into consideration for sampling errors. Indeed, the observed differences between areas (or points in the map) are not directly interpretable, as they derive from the composition of true, structural differences and of the noise deriving from the sampling process. This problem is well known in human epidemiology, and several solutions have been proposed to filter the signal from the noise. These statistical methods are usually referred to as Disease Mapping. In geographical analysis a first goal is to evaluate the statistical significance of the heterogeneity between areas (or points). If the test indicates rejection of the hypothesis of homogeneity the following task is to study the spatial pattern of the disease. The spatial variability of risk is usually decomposed into two terms: a spatially structured (clustering) and a non spatially structured (heterogeneity) one. The heterogeneity term reflects spatial variability due to intrinsic characteristics of the sampling units (e.g. igienic conditions of farms), while the clustering term models the association due to proximity between sampling units, that usually depends on ecological conditions that vary over the study area and that affect in similar way breedings that are close to each other. Hierarchical bayesian models are the main tool to make inference over the clustering and heterogeneity components. The results are based on the marginal posterior distributions of the parameters of the model, that are approximated by Monte Carlo Markov Chain methods. Different models can be defined depending on the terms that are considered, namely a model with only the clustering term, a model with only the heterogeneity term and a model where both are included. Model selection criteria based on a compromise between degree of complexity and goodness of fit are then needed to discriminate among them, because each specification has a different biological meaning. Our aim is to demonstrate that these techniques can be used to study the geographical distribution of a parasite infection. Our analyses are based on data collected in 142 farms of the province of Latina. In each breeding a fixed number of sheeps has been sampled (20) and checked for the presence of C. daubneyi. We have specified a Binomial model for the proportion of infected animals in each breeding. The heterogeneity component is modelled in a standard way, while we have used different prior specifications for the clustering term to show how they affect the results. When we use the usual specification also for clustering, the two models show a completely different spatial pattern of infection, probably because the intrinsic spatial structure of the clustering term tend to bias our inferences. The selection criterion indicates in this case the heterogeneity model as the "best" one. However, if we modify the prior so that a lower degree of spatial interaction is assumed, the clustering model is less complex and its goodness of fit better and it should be preferred.

Animal Husbandry↗

Modification of the kitten's visual cortex by exposure to spatially periodic patterns.

Kittens were dark-reared except for exposure to three types of spatially periodic, vertically striped pattern: 1. single, widely spaced black bars; 2. wide areas of regular vertical grating separated by large blank patches; 3. a uniform, continuous grating with a spatial frequency of 0.5 c/deg. In each case there was a bias towards vertical in the distribution of preferred orientations of cells recorded in the visual cortex. The contrast sensitivity of individual neurones for gratings of different spatial frequencies was analysed quantitatively. In kittens exposed to a uniform grating of 0.5 c/deg, many cells were maximally sensitive close to 0.5 c/deg, as they are in normal cats. The occipital potential evoked by vertical gratings higher in frequency than 0.3 c/deg was consistently greater in amplitude than that for horizontal, and a vertical grating of 0.5 c/deg produced the maximum activity. These results are compared with those of Maffei and Fiorentini (1974); the differences between our results and theirs may be attributable to the degree of variability in spatial frequency and orientation during rearing, and to the duration of exposure.

Animals↗

Spatially fixed patterns account for the spike and wave features in absence seizures.

Despite genetic, morphological and experimental in vivo, data implying fixed abnormalities in patients with absence seizures, attempts to find highly consistent features in the 3-Hz spike-and-wave pattern recorded during sequential seizures from the same subject have been largely unsuccessful. We used a new data decomposition technique called Independent Component Analysis (ICA) to separate multiple spike-and-wave episodes in the EEG recorded from five subjects with absence seizures into multiple consistent components. Each component corresponded to a temporally-independent waveform and a fixed spatial distribution. Almost all components separated by the ICA algorithm had overlapping, largely frontal spatial distributions. The analysis unmasked 5-8 components from each subject that were consistently activated across all seizures, with no components detected that were selectively activated by one seizure and not another. The "spike" and "wave" features noted in the EEG of every subject were each separated by the ICA algorithm into two or more components. Other components were active only at the beginning of each seizure or were related to ongoing brain activity not directly related to the 3Hz spike-and-wave pattern. By contrast randomly selected spatial patterns used for data decomposition resulted in components that were uninformative, similar to simply changing the montage for viewing the EEG. Our results suggest that despite previously described variability in the raw EEG, certain highly specific spatial distributions of activation are reproducible across seizures. These may reflect ictal and non-ictal brain activity consistently activating the same group of neurons.

Action Potentials↗

The effect of location on the discrimination of spatial vibrotactile patterns.

The present study examined whether the locations of patterns on the skin affected the ability to process information about their shapes. In Experiment 1, pairs of spatial vibrotactile patterns, using the array from the Optacon, were presented sequentially to subjects' left index fingerpads. The location of each pattern in a pair was varied randomly among four locations on the skin. The subjects responded "same" or "different" on the basis of the shapes of patterns, regardless of their locations. Discrimination accuracy was highest and response time fastest when patterns occupied identical locations (ILs), and performance suffered with increasing distance between patterns. In Experiment 2, pairs were presented to corresponding points or to noncorresponding points on separate fingerpads. When patterns occupied corresponding points on separate fingers, accuracy was lower than when patterns occupied ILs on a single finger, but higher than when patterns occupied noncorresponding points on separate fingers. The results suggested that discriminability declined partly because patterns did not occupy ILs, and partly because separate locations had different densities of innervation.

Adult↗

Peroxidase and superoxide dismutase activities in fig leaves in response to ambient air pollution in a subtropical city.

Urban air pollution is a serious problem in both developing and developed countries, and antioxidant enzyme activities in plants have been suggested as a useful bioindicator of air pollution. In this study, the seasonal and spatial variability of peroxidase and superoxide dismutase activities were measured in leaves of Ficus microcarpa at eight sampling sites in the Taipei metropolitan area and one background site in rural area at each month for a year. The spatial pattern of peroxidase activity in figs collected from the Taipei metropolitan area was similar to the spatial pattern of O3 concentration in the Taipei metropolitan area. The peroxidase activities of Ficus microcarpa were significantly higher at sampling sites from the outer zone of the metropolitan area than those from the inner zone of the metropolitan area in spring and summer. On the other hand, the spatial pattern of superoxide dismutase activity in fig leaves did not show significant differences between the inner and outer zones of the Taipei metropolitan area. In addition, peroxidase activities, but not superoxide dismutase activities, of Ficus microcarpa were significantly higher in sites with high traffic density than those in low traffic density sites. Even though peroxidase activities in Ficus microcarpa tended to be higher in high traffic density sites or some sites with high ozone concentration, site-specific changes of peroxidase activity in Ficus microcarpa due to O3 pollution were not clearly observed in this study. Based on these results, neither peroxidase nor superoxide dismutase in Ficus microcarpa is a sensitive bioindicator for O3 pollution, although peroxidase shows some potential to be used as a general bioindicator of air quality.

Air Pollutants↗

Evoked potentials and simple motor reaction times to localized visual patterns.

Spatially localized, contrast modulated visual stimuli evoke a monophasic, inion negative scalp potential (VEP) which can be recorded simultaneously with motor responses in simple reaction time experiments. VEP response time and median motor response latency are linearly related over a wide range of stimuli. We interpret our results to suggest that VEPs and motor response latencies arise from a common sensory system with different thresholds for detection and reaction. A model is introduced to predict detection thresholds from VEP response times which are usually more robust measures than VEP amplitudes.

Contrast Sensitivity↗

Patterning of the embryo: the first spatial decisions in the life of a mouse.

Although in most species the polarity of the embryo takes its roots from the spatial patterning of the egg, mammals were viewed as an exception. This was because the anteroposterior polarity of the mouse embryo could not be seen until gastrulation, and no developmental cues were known that could define polarity at earlier stages. Why should we now re-consider this view? While mechanisms of axis formation in mammals could, in principle, be unique, the evolutionary conservation of numerous other developmental processes raises the question of why mammals would have evolved a different way or timing of organising their embryonic polarity. Indeed, recent evidence shows that well before the onset of gastrulation, the mouse embryo initiates asymmetric patterns of gene expression in its visceral endoderm. Although this extra-embryonic tissue does not contribute to the body itself, it is involved in axis formation. Other recent work has revealed that spatial distribution of cells in the visceral endoderm can be traced back to polarity present at the blastocyst stage. These insights have raised the possibility that embryonic polarity might also originate early during development of mammalian embryos. Indeed it now appears that there are at least two spatial cues that operate in the mouse egg to shape polarity of the blastocyst. One of these is at the animal pole, which is defined by the site of female meiosis, and another is associated with the position of sperm entry. In this review I discuss these recent findings, which have led to the recognition that mouse embryos initiate development of their polarity at the earliest stages of their life. This novel perspective raises questions about the nature of cellular and molecular mechanisms that could convert developmental cues in the zygote to axes of the blastocyst, and hence into polarity of the post-implantation embryo. It also brings to light the need to understand how such mechanisms could enable early mouse development to be so regulative.

Animals↗

Socio-demographic trends in Northern Ireland, 1971 to 1991.

"Northern Ireland has demographic and socio-economic structures which set it apart from the rest of the United Kingdom and religion impacts on this social demography more than in any other 'developed' society. Peripherality also serves to underpin some of the distinctiveness of the Province. Socio-economic and demographic data from Population Censuses and demographic data from Annual Reports of the Registrar General are analysed. The socio-demographic trends between 1971, 1981 and 1991 are traced and the spatial patterns are described. Many of the spatial patterns have been remarkably persistent over time and the problems that arise from this are unlikely to be addressed fully given the Province's perverse polity."

Demography↗